The induction of cytodifferentiation and tissue pattern development in many epithelial organs is mediated by epithelial-mesenchymal interactions. Recent studies have implicated direct intercellular contacts at the epithelial-mesenchymal interface in these inductive phenomena. The present project will investigate the morphologic mechanisms of information transfer which occur at the epithelial- mesenchymal interface in developing salivary glands and tooth germs. The study will involve a detailed ultrastructural study of the nature of these contact zones both in vivo and in vitro. Additionally, functional differentiation of embryonic salivary and tooth germ epithelium will be investigated ultrastructurally in an in vitro transfilter system. This system will be manipulated to selectively block direct epithelial- mesenchymal contacts while allowing the free exchange of macromolecules between these tissues to determine if functional differentiation of these epithelia can occur in the absence of direct contacts at the epithelial-mesenchymal interface. Finally, ultrastructural studies of the epithelial-mesenchymal interface of salivary and enamel organ epithelium cultured on altered or ectopic dermis will help determine if the cytologic and tissue pattern abnormalities observed in such systems can be attributed to abberations in the normal morphology of the epithelial-mesenchymal interface. This area of investigation is important in that the understanding of the mechanisms of information transfer between tissues of dissimilar origin is fundamental to understanding such problems as birth defects and cancer. In this regard, epithelial-mesenchymal contacts of the type being studied by the present proposal have been observed in human tumors and in experimental neoplasms.